1. Field of the Invention
This invention relates to pyridylphenyl nitrogen heterocycle-substituted carbinols, pharmaceutical compositions containing them, methods of using them to treat inflammatory disease in mammals and processes for preparing said compounds.
2. Background
Inflammatory diseases are a widespread cause of human suffering and loss of function. Additionally, the treatment of patients with these diseases represents a very large expense in terms of money, facilities and personnel. The incidence of many such diseases is expected to rise in the future as life expectancy and the median age of the population continue to increase.
Inflammatory diseases are known which affect many diverse tissues and organs in the body. Examples of diseases in which the inflammation is most apparent in the joints and related connective tissue are diseases such as osteoarthritis, rheumatoid arthritis, tendonitis and bursitis. These diseases are most often treated with nonsteroidal anti-inflammatory agents such as aspirin, ibuprofen, and piroxicam, or with anti-inflammatory glucocorticosteroids. However, these treatments are deficient either due to a lack of efficacy in completely controlling the disease process, or due to unacceptable toxic side effects. Rheumatoid arthritis in particular is a representative of a class of systemic diseases thought to possess an auto-immunity component, which are treated additionally with anti-proliferative agents and with so-called disease-modifying agents such as gold salts, penicillamine and antimalarial agents. These drugs also possess severe toxic effects which limit their utility.
Examples of diseases in which the inflammation is most apparent in the skin are psoriasis, contact dermatitis, atopic dermatitis, and eczema. These diseases are usually treated with anti-inflammatory glucocorticosteroids, or (in the case of psoriasis) with psoralen in combination with UV-A light (PUVA), or with coal tar preparations or antiproliferative agents. Again, these treatments are often unacceptable to patients and also have a poor degree of efficacy and/or unacceptable side effects.
Inflammatory diseases of other tissues and organs are also of concern, for example inflammatory bowel disease and ocular inflammation such as uveitis and conjunctivitis. Treatments for these diseases, primarily using glucocorticosteroids, also lack efficacy and freedom from toxic effects.
Thus, there is a continuing medical need for safe, efficacious anti-inflammatory agents for use as systemic and/or topical therapy for inflammatory diseases.